PB2032: MAGNETISMM-9: AN OPEN-LABEL, MULTICENTER, NON-RANDOMIZED PHASE 1/2 STUDY OF ELRANATAMAB IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA
Authors: R. Fonseca, J. Kuroda, T. Ishida, R. Popat, J. S. Huang, A. Yver, E. Vandendries, M. Elmeliegy, W. D. Ma, D. W. Sborov
Journal: HemaSphere (2022)

Background: Elranatamab (PF-06863135) is a humanized bispecific antibody that targets both B cell maturation antigen (BCMA) on multiple myeloma (MM) cells and CD3 on T cells resulting in T cell- mediated cytotoxicity. In preclinical studies, elranatamab has demonstrated anti-myeloma activity and delayed disease progression. In the ongoing phase 1 MagnetisMM-1 study, elranatamab has demonstrated clinical efficacy and a manageable safety profile in patients with relapsed/refractory MM (Bahlis et al, J Clin Oncol 2021). Elranatamab maximum tolerated dose has not yet been reached. Subcutaneous elranatamab at the recommended dose of 76 mg once weekly on a 28-day cycle with a 2 step-up priming dose regimen administered during the first week is currently being evaluated in a phase 2 study, MagnetisMM-3 (Lesokhin et al, Blood, 2021). Aims: To evaluate an alternative priming regimen to further mitigate cytokine release syndrome incidence and severity, and to evaluate subcutaneous elranatamab every 2 weeks and every 4 weeks in patients with relapsed/refractory MM. Methods: MagnetisMM-9 (start date: October 2021; estimated completion date: April 2025) is an open-label, multicenter, non-randomized phase 1/2 study. In part 1 of the study, patients will receive premedications and 2 step-up priming doses on cycle 1 day 1 (4 mg) and day 4 (20 mg), followed by elranatamab 76 mg once weekly for 6 cycles, and a dose every 2 weeks thereafter if partial response or better is achieved and maintained. In part 2, higher doses of elranatamab (>76 mg) at increased intervals between doses will be evaluated. The primary endpoint is grade ≥2 cytokine release syndrome rate during cycle 1. Secondary endpoints include dose-limiting toxicities (part 2 only), objective response rate, duration of response, progression-free survival, overall survival, minimal residual disease negativity rate, safety, and pharmacokinetics. Eligible patients should be 18 years of age or older with a MM diagnosis and measurable disease according to International Myeloma Working Group criteria, refractory to at least one proteasome inhibitor, one immunomodulatory drug, and one anti-CD38 antibody, relapsed/refractory to their last treatment regimen, and have an Eastern Cooperative Oncology Group performance status ≤1. Key exclusion criteria are smoldering MM, active plasma cell leukemia, amyloidosis, POEMS syndrome, stem cell transplant within 12 weeks of enrollment, active, uncontrolled bacterial, fungal, or viral infections, or any other active malignancy within 3 years prior to enrollment (except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ), or previous treatment with an anti-BCMA bispecific antibody. The study is open at centers in the USA, UK, Japan, and Taiwan. ClinicalTrials.gov ID: NCT05014412. Results: Results not available (trial-in-progress) Summary/Conclusion: Conclusion not available (trial-in-progress)